Abstract
Hepatocellular carcinoma (HCC) is a serious healthcare problem worldwide because of its increasing morbidity and high mortality rates. However, our understanding of the mechanism of liver tumorigenesis remains incomplete. We report the expression of myosin light chain kinase (MLCK) in the livers of rats with diethylnitrosamine (DENA)-induced HCC and investigated the correlation between MLCK and liver tumorigenesis by observing the expression of MLCK in a rat model of HCC. HCC was induced in rats by an intraperitoneal injection of DENA, and resveratrol-treated rats were orally administered resveratrol with 50 mg/kg body weight/day. The livers of rats were excised after 20 weeks and immersed in 10% formaldehyde prior to immunohistochemical and Western blot analyses for determining the level of MLCK expression. These analyses indicated that the MLCK expression was higher in the livers of HCC rats than in normal and resveratrol-treated rats. High level of MLCK expression was responsible for proliferation and anti-apoptotic effects. However, resveratrol down-regulated the expression of MLCK, which induced cell apoptosis and inhibited liver tumorigenesis in rats with DENA-induced HCC. Our results suggest that the over expression of MLCK may be related to the development of liver tumorigenesis.
Highlights
Hepatocellular carcinoma (HCC), the most common type of liver cancer, is the fifth most common malignant tumor type worldwide and the second leading cause of cancer-related death [1,2]
This study provides the first in vivo evidence that the over expression of myosin light chain kinase (MLCK) is associated with the initiation of HCC by reducing tumor cell apoptosis and that the inhibition of MLCK by resveratrol induces apoptosis and prevents liver tumorigenesis (Figures 2–4)
Our study has clearly shown that resveratrol down-regulates the expression of MLCK, resveratrol could be useful for the prevention of HCC
Summary
Hepatocellular carcinoma (HCC), the most common type of liver cancer, is the fifth most common malignant tumor type worldwide and the second leading cause of cancer-related death [1,2]. Interactions between cells and extracellular matrix (ECM) play an important role in development and normal cellular function. Cell adhesion to ECM is a key factor in cellular homeostasis, and the disruption of such interactions leads to a specific type of apoptosis known as “anoikis” in most non-transformed cell types. Integrin-mediated cell migration requires the contractile forces generated by the actin cytoskeleton that are mediated by the actin/myosin network through integrin-ECM interactions. Additional studies have shown that MLCK is involved in other key aspects of tumorigenesis, including the growth of primary tumors and tumor cell motility in human pancreatic cancer cells and Mm5MT mouse mammary tumor cells [25,26]. The relationship between MLCK and HCC is described, the variable expression of MLCK during the development of HCC and the effects of resveratrol on DENA-induced hepatocarcinogensis, apoptosis and MLCK expression are investigated
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